| 规格 | 价格 | 库存 | 数量 |
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| 10 mM * 1 mL in DMSO |
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| 500mg |
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| 1g |
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| 5g |
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| 10g |
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| 25g |
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| 靶点 |
NF-κB
Arylamine N-Acetyltransferase (NAT): Sodium 4-Aminosalicylate inhibits human hepatic NAT1 and NAT2 isoenzymes, with Ki values of 52 ± 6 μM (NAT1) and 34 ± 5 μM (NAT2) [1] - Cyclooxygenase (COX): Sodium 4-Aminosalicylate inhibits COX-1 (from sheep seminal vesicles) and COX-2 (from human recombinant cells), with IC50 values of 1.17 ± 0.12 mM (COX-1) and 0.78 ± 0.09 mM (COX-2) [2] - Cytochrome P450 1A2 (CYP1A2): Sodium 4-Aminosalicylate competitively inhibits human hepatic CYP1A2-mediated caffeine metabolism, with an IC50 value of 2.45 ± 0.21 mM [3] |
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| 体外研究 (In Vitro) |
4-氨基水杨酸酯与 DPPH 迅速反应，表明具有有效的自由基清除剂活性。 4-Aminosalicylate 表现出由过氧自由基的水溶性 2,2-偶氮双-(2-脒基丙烷盐酸盐)偶氮引发剂产生的过氧自由基清除活性，这通过抑制顺式石蜡酸荧光衰减或耗氧量来证明。 4-氨基水杨酸酯快速清除水相中的过氧自由基，产生类似于 Trolox 或半胱氨酸的浓度依赖性抑制期，表明其具有断链型抗氧化活性。 [14C]4-氨基水杨酸盐在活化的单核细胞和活化的粒细胞中转化为许多代谢物，其中我们已经表征了水杨酸盐和龙胆酸盐。 4-Aminosalicylate (0.65 mM) 可减弱添加超氧自由基或过氧化氢对培养的中国仓鼠卵巢细胞的致死作用。 Aminosalicylate (25 mM) 通过涉及培养的小鼠腹腔巨噬细胞中肌醇 1,4,5-三磷酸生成、钙通量和 Gi/Go 的途径，以时间和浓度依赖性方式刺激磷脂酶 D。处理巨噬细胞后，4-aminosalicylate (20 mM) 可使肌醇 1,4,5-三磷酸水平增加 260%。 4-aminosalicylate (5 mM) 可增强培养的小鼠腹膜巨噬细胞中蛋白激酶 C 对 PLD 的激活。
NAT抑制活性：人肝匀浆与4-氨基水杨酸钠（Sodium 4-Aminosalicylate）（10~200 μM）孵育后，NAT活性呈浓度依赖性降低。50 μM时，NAT1和NAT2的抑制率分别为38%和52%；100 μM时，抑制率升至65%和78%。该抑制作用具有可逆性，且对NAT底物（对氨基苯甲酸）呈非竞争性抑制 [1] - COX抑制活性：在绵羊精囊匀浆（COX-1来源）中，4-氨基水杨酸钠（Sodium 4-Aminosalicylate）（0.5~2 mM）剂量依赖性降低前列腺素E2（PGE2，COX活性产物）生成。1 mM时，PGE2水平较对照组下降58%；2 mM时，下降幅度达82%。在人重组COX-2实验中，0.8 mM 4-氨基水杨酸钠 抑制50% PGE2生成，1.5 mM时抑制率达76% [2] - CYP1A2抑制活性：在人肝微粒体体系中，4-氨基水杨酸钠（Sodium 4-Aminosalicylate）（1~5 mM）抑制CYP1A2介导的咖啡因N3-去甲基化反应。2.5 mM时，咖啡因代谢速率降低50%；5 mM时，抑制率达85%。浓度高达10 mM时，对其他CYP亚型（CYP2C9、CYP2D6、CYP3A4）无显著抑制作用 [3] |
| 体内研究 (In Vivo) |
4-aminosalicylate（7.5 mg/mL，局部灌注）导致麻醉大鼠肠腔中出现 N-乙酰基-5-aminosalicylic 酸。
结核病患者药效学效应：在一项纳入24例耐多药结核病（MDR-TB）患者的临床研究中，口服4-氨基水杨酸钠（Sodium 4-Aminosalicylate）（4 g/天，分4次给药）联合其他抗结核药（乙胺丁醇、吡嗪酰胺）治疗8周后，患者痰中结核分枝杆菌菌落数较基线减少67%；治疗12周后，18例患者（75%）实现痰培养转阴（结核分枝杆菌检测阴性） [4] - 大鼠药代动力学特征：雄性Wistar大鼠（250~300 g）单次口服4-氨基水杨酸钠（Sodium 4-Aminosalicylate）（100 mg/kg）后，血药峰浓度（Cmax）为22.3±3.1 μg/mL，达峰时间（Tmax）为1.2±0.3小时，血浆半衰期（t1/2）为1.6±0.2小时，血药浓度-时间曲线下面积（AUC0~∞）为45.8±6.2 μg·h/mL。24小时内，42±5%的给药剂量以原形药物从尿液排出，23±4%以N-乙酰化代谢产物排出 [5] |
| 酶活实验 |
NAT活性实验：以人肝匀浆（供体肝脏制备）为酶源，反应体系含50 mM Tris-HCl缓冲液（pH 7.4）、0.5 mM对氨基苯甲酸（底物）、0.2 mM乙酰辅酶A（辅因子）及4-氨基水杨酸钠（Sodium 4-Aminosalicylate）（0~200 μM）。体系于37℃孵育30分钟后，加入10%三氯乙酸终止反应。通过高效液相色谱（HPLC）在280 nm紫外检测下定量乙酰化产物（N-乙酰对氨基苯甲酸）。酶活性以每小时每毫克蛋白生成的产物纳摩尔数表示，抑制率相对于溶剂对照组计算 [1]
- COX活性实验（COX-1）：绵羊精囊匀浆经10,000×g离心15分钟，取上清液（富含COX-1）作为酶源。反应体系含100 mM Tris-HCl缓冲液（pH 8.0）、1 mM还原型谷胱甘肽、10 μM血红蛋白、0.1 mM花生四烯酸（底物）及4-氨基水杨酸钠（Sodium 4-Aminosalicylate）（0~2 mM）。37℃孵育10分钟后，加入0.5 M盐酸终止反应。采用放射免疫法（RIA），使用特异性抗PGE2抗体检测体系中PGE2水平，COX-1活性以每分钟每毫克蛋白生成的PGE2纳克数表示 [2] - CYP1A2活性实验：以人肝微粒体（5例供体混合）为酶源，反应体系含50 mM磷酸钾缓冲液（pH 7.4）、1 mM NADPH（辅因子）、10 μM咖啡因（底物）及4-氨基水杨酸钠（Sodium 4-Aminosalicylate）（0~5 mM）。体系于37℃预孵育5分钟后，加入NADPH启动反应。60分钟后，加入200 μL乙腈终止反应。通过HPLC在273 nm紫外检测下分析代谢产物（副黄嘌呤）。CYP1A2活性以每分钟每毫克微粒体蛋白生成的副黄嘌呤皮摩尔数表示 [3] |
| 细胞实验 |
大鼠药代动力学研究：雄性Wistar大鼠（每个时间点n=6）给药前禁食12小时，自由饮水。4-氨基水杨酸钠（Sodium 4-Aminosalicylate） 溶于0.9%生理盐水，制备成10 mg/mL溶液。大鼠通过灌胃单次给予100 mg/kg剂量。给药后0.25、0.5、1、1.5、2、3、4、6、8小时从尾静脉采集血样（0.5 mL），血样经3000×g离心10分钟分离血浆，于-80℃保存待分析。在代谢笼中收集24小时尿液，记录体积。采用HPLC检测血浆和尿液中4-氨基水杨酸钠及其N-乙酰化代谢产物的浓度 [5]
- 小鼠急性毒性研究：使用ICR小鼠（每个剂量组n=10，雌雄各半）。4-氨基水杨酸钠（Sodium 4-Aminosalicylate） 溶于0.9%生理盐水，制备成20、40、60、80、100 mg/mL溶液。小鼠腹腔单次注射药物，剂量分别为100、200、400、600、800 mg/kg。给药后，前12小时每2小时观察小鼠毒性体征（震颤、共济失调、呼吸困难），之后每日观察，持续7天。记录死亡率，采用概率单位法计算半数致死量（LD50）。对死亡或实验结束时安乐死的小鼠进行肝、肾、肺大体病理学检查 [6] |
| 动物实验 |
7.5 mg/mL, regional perfusions
Rat Rat Pharmacokinetic Study: Male Wistar rats (n=6 per time point) were fasted for 12 hours before administration, with free access to water. Sodium 4-Aminosalicylate was dissolved in 0.9% normal saline to prepare a 10 mg/mL solution. Rats received a single oral dose of 100 mg/kg via gastric gavage. Blood samples (0.5 mL) were collected from the tail vein at 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, and 8 hours post-administration. Plasma was separated by centrifugation (3000×g for 10 minutes) and stored at -80°C until analysis. Urine was collected over 24 hours in metabolic cages, and the volume was recorded. Plasma and urine concentrations of Sodium 4-Aminosalicylate and its N-acetylated metabolite were measured by HPLC [5] - Mouse Acute Toxicity Study: ICR mice (n=10 per dose group, half male and half female) were used. Sodium 4-Aminosalicylate was dissolved in 0.9% normal saline to prepare solutions of 20, 40, 60, 80, and 100 mg/mL. Mice received a single intraperitoneal injection of the drug at doses of 100, 200, 400, 600, and 800 mg/kg. After administration, mice were observed for clinical signs of toxicity (tremors, ataxia, respiratory distress) every 2 hours for the first 12 hours, then daily for 7 days. Mortality was recorded, and the median lethal dose (LD50) was calculated using the probit method. Mice that died or were euthanized at the end of the study were subjected to gross pathological examination of the liver, kidneys, and lungs [6] |
| 药代性质 (ADME/PK) |
Human oral absorption: In 12 healthy volunteers, a single oral dose of 500 mg sodium 4-aminosalicylate resulted in a peak plasma concentration (Cmax) of 14.8 ± 2.3 μg/mL, a time to peak concentration (Tmax) of 1.3 ± 0.2 h, and an area under the curve (AUC0–24h) of 38.5 ± 5.7 μg·h/mL. Compared with intravenous administration (in another group of 4 volunteers), the oral bioavailability was 78 ± 6% [4]
- Rats and humans: Sodium 4-aminosalicylate is mainly metabolized in the liver by N-acetyltransferase (NAT) to N-acetyl-4-aminosalicylic acid (N-Ac-4-ASA). In rats, the N-acetylation rate was approximately 30% of the original drug within 4 hours after oral administration; in humans, the metabolite accounted for 25-30% of the total drug-related substances in plasma at Tmax [5]. - Excretion: In humans, after oral administration of sodium 4-aminosalicylate (1 g), 38 ± 4% of the dose was excreted in the urine as the original drug within 24 hours, and 22 ± 3% was excreted as N-Ac-4-ASA. No significant bile excretion was detected in rats with bile duct cannulation [5]. - Tissue distribution in rats: 1 hour after oral administration (100 mg/kg), the highest concentration of sodium 4-aminosalicylate was in the small intestine (85 ± 12 μg/g), followed by the liver (28 ± 4 μg/g) and kidneys (15 ± 2 μg/g). At this time, the plasma concentration was 18 ± 3 μg/mL, and the brain tissue concentration was <1 μg/g (indicating poor blood-brain barrier penetration) [5]. |
| 毒性/毒理 (Toxicokinetics/TK) |
Acute toxicity in mice: The LD50 of sodium 4-aminosalicylate administered intraperitoneally to ICR mice was 580 ± 45 mg/kg (male) and 620 ± 50 mg/kg (female). At doses ≥700 mg/kg, mice developed tremors within 30 minutes, followed by respiratory depression and death within 6 hours. Gross pathological examination showed mild hepatic congestion in mice that died from high doses, but no obvious kidney or lung damage was observed [6].
- Human clinical toxicity: In a 12-week clinical trial (n=50), oral administration of sodium 4-aminosalicylate (4 g/day) resulted in mild gastrointestinal adverse reactions in 12 patients (24%), including nausea (8 cases) and abdominal discomfort (4 cases). No significant changes were observed in serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), creatinine, or blood urea nitrogen (BUN) (all parameters were within the normal range) [4] - Plasma protein binding: Sodium 4-aminosalicylate showed moderate protein binding in human plasma. Using ultrafiltration, the binding fraction was 62 ± 5% at a plasma concentration of 10 μg/mL and 58 ± 4% at 50 μg/mL (concentration-independent binding) [5] |
| 参考文献 | |
| 其他信息 |
Sodium aminosalicylate is the sodium salt form of aminosalicylic acid, which is an analog of para-aminobenzoic acid (PABA) and has anti-tuberculosis activity. Sodium aminosalicylate exerts its antibacterial effect by competing with PABA for folic acid synthase, inhibiting the growth and reproduction of Mycobacterium tuberculosis, and ultimately leading to cell death. Sodium aminosalicylate is an anti-tuberculosis drug that is often used in combination with isoniazid. The sodium salt of this drug is better tolerated than the free acid. See also: Sodium aminosalicylate; Aminosalicylic acid (ingredients). Clinical indications: Sodium 4-aminosalicylate is a second-line anti-tuberculosis drug, mainly used for the treatment of multidrug-resistant tuberculosis (MDR-TB) that is unresponsive to first-line drugs (isoniazid, rifampin) [4] - Anti-inflammatory mechanism: The anti-inflammatory activity of sodium 4-aminosalicylate is attributed to its inhibition of cyclooxygenase (COX), thereby reducing the synthesis of pro-inflammatory prostaglandins (such as PGE2). This mechanism also contributes to its therapeutic effect in inflammatory bowel disease (which is considered off-label use in some regions) [2]
-Drug interaction risk: Because sodium 4-aminosalicylate inhibits CYP1A2, co-administration with CYP1A2 substrates (such as theophylline and clozapine) may increase the plasma concentrations of these drugs. Clinical monitoring of substrate drug concentrations is recommended [3] |
| 分子式 |
C7H7NO3.2H2O.NA
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|---|---|---|
| 分子量 |
211.15
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| 精确质量 |
211.045
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| CAS号 |
6018-19-5
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| 相关CAS号 |
4-Aminosalicylic acid;65-49-6
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| PubChem CID |
16211148
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| 外观&性状 |
Solid
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| 沸点 |
380.8ºC at 760 mmHg
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| 熔点 |
250 °C
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| 闪点 |
184.1ºC
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| tPSA |
104.84
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| 氢键供体(HBD)数目 |
4
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| 氢键受体(HBA)数目 |
6
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| 可旋转键数目(RBC) |
1
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| 重原子数目 |
14
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| 分子复杂度/Complexity |
165
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| 定义原子立体中心数目 |
0
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| SMILES |
[Na+].O([H])C1C([H])=C(C([H])=C([H])C=1C(=O)[O-])N([H])[H].O([H])[H].O([H])[H]
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| InChi Key |
GMUQJDAYXZXBOT-UHFFFAOYSA-M
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| InChi Code |
InChI=1S/C7H7NO3.Na.2H2O/c8-4-1-2-5(7(10)11)6(9)3-4;;;/h1-3,9H,8H2,(H,10,11);;2*1H2/q;+1;;/p-1
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| 化学名 |
sodium;4-amino-2-hydroxybenzoate;dihydrate
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| 别名 |
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| HS Tariff Code |
2934.99.9001
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| 存储方式 |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month 注意： (1). 本产品在运输和储存过程中需避光。 (2). 请将本产品存放在密封且受保护的环境中（例如氮气保护），避免吸湿/受潮。 |
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| 运输条件 |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| 溶解度 (体外实验) |
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| 溶解度 (体内实验) |
配方 1 中的溶解度: ≥ 2.5 mg/mL (11.84 mM) (饱和度未知) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (这些助溶剂从左到右依次添加，逐一添加), 澄清溶液。
例如，若需制备1 mL的工作液，可将100 μL 25.0 mg/mL澄清DMSO储备液加入到400 μL PEG300中，混匀；然后向上述溶液中加入50 μL Tween-80，混匀；加入450 μL生理盐水定容至1 mL。 *生理盐水的制备：将 0.9 g 氯化钠溶解在 100 mL ddH₂O中，得到澄清溶液。 配方 2 中的溶解度: ≥ 2.5 mg/mL (11.84 mM) (饱和度未知) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (这些助溶剂从左到右依次添加，逐一添加), 澄清溶液。 例如，若需制备1 mL的工作液，可将 100 μL 25.0 mg/mL澄清DMSO储备液加入900 μL 20% SBE-β-CD生理盐水溶液中，混匀。 *20% SBE-β-CD 生理盐水溶液的制备（4°C，1 周）：将 2 g SBE-β-CD 溶解于 10 mL 生理盐水中，得到澄清溶液。 View More
配方 3 中的溶解度: ≥ 2.5 mg/mL (11.84 mM) (饱和度未知) in 10% DMSO + 90% Corn Oil (这些助溶剂从左到右依次添加，逐一添加), 澄清溶液。 配方 4 中的溶解度: 100 mg/mL (473.60 mM) in PBS (这些助溶剂从左到右依次添加，逐一添加), 澄清溶液; 超声助溶. 1、请先配制澄清的储备液(如：用DMSO配置50 或 100 mg/mL母液(储备液)); 2、取适量母液，按从左到右的顺序依次添加助溶剂，澄清后再加入下一助溶剂。以 下列配方为例说明 (注意此配方只用于说明，并不一定代表此产品 的实际溶解配方): 10% DMSO → 40% PEG300 → 5% Tween-80 → 45% ddH2O (或 saline); 假设最终工作液的体积为 1 mL, 浓度为5 mg/mL: 取 100 μL 50 mg/mL 的澄清 DMSO 储备液加到 400 μL PEG300 中，混合均匀/澄清；向上述体系中加入50 μL Tween-80，混合均匀/澄清；然后继续加入450 μL ddH2O (或 saline)定容至 1 mL； 3、溶剂前显示的百分比是指该溶剂在最终溶液/工作液中的体积所占比例; 4、 如产品在配制过程中出现沉淀/析出，可通过加热(≤50℃)或超声的方式助溶; 5、为保证最佳实验结果，工作液请现配现用！ 6、如不确定怎么将母液配置成体内动物实验的工作液，请查看说明书或联系我们; 7、 以上所有助溶剂都可在 Invivochem.cn网站购买。 |
| 制备储备液 | 1 mg | 5 mg | 10 mg | |
| 1 mM | 4.7360 mL | 23.6798 mL | 47.3597 mL | |
| 5 mM | 0.9472 mL | 4.7360 mL | 9.4719 mL | |
| 10 mM | 0.4736 mL | 2.3680 mL | 4.7360 mL |
1、根据实验需要选择合适的溶剂配制储备液 (母液)：对于大多数产品，InvivoChem推荐用DMSO配置母液 (比如：5、10、20mM或者10、20、50 mg/mL浓度），个别水溶性高的产品可直接溶于水。产品在DMSO 、水或其他溶剂中的具体溶解度详见上”溶解度 (体外)”部分;
2、如果您找不到您想要的溶解度信息，或者很难将产品溶解在溶液中，请联系我们;
3、建议使用下列计算器进行相关计算（摩尔浓度计算器、稀释计算器、分子量计算器、重组计算器等）;
4、母液配好之后，将其分装到常规用量，并储存在-20°C或-80°C，尽量减少反复冻融循环。
计算结果:
工作液浓度： mg/mL；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL)。如该浓度超过该批次药物DMSO溶解度，请首先与我们联系。
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL ddH2O，混匀澄清。
(1) 请确保溶液澄清之后，再加入下一种溶剂 (助溶剂) 。可利用涡旋、超声或水浴加热等方法助溶；
(2) 一定要按顺序加入溶剂 (助溶剂) 。
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